Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the world, causing serious adverse events on women's reproductive health including complications of pregnancy, pelvic inflammatory disease and infertility. The objectives of this project are to define the epidemiology, risk factors, transmission kinetics, and pathogenesis of C. trachomatis infections in different population settings and in different disease states. In a multi-center international trial of 5,000 participants, we screened for a variety of STDs using non-invasive molecular amplified assays. Prevalence of chlamydia in young women was 12.2% in China, 0.1% in India, 6.4% in Peru, 10.4% in Russia, and 2.5% in Zimbabwe. Gonorrhea prevalence was <1.5% in all five countries. Serologic evidence for HSV-2 infection ranged from 9 to 20% among women in all countries except Zimbabwe, where the prevalence among women was 59%. These data have important implications for the future of the HIV epidemics because of the strong association of STDs, particularly HSV-2, for HIV acquisition. We have used the Internet to offer sampling for chlamydia for >2000 women at home using self-obtained vaginal swabs. Over 90% preferred to collect their own sample, with 96.7% indicating the collection was easy/very easy. Prevalence has been 15.3% in young women age 15-19 yr. Both young age and Black race were statistically associated with chlamydia positivity. We have extended Internet screening to over 500 males with self-collected penile swabs and urines: 106 (21%) were positive for at least one STI, 64 (13%) for chlamydia, 4 (1%) for gonorrhea, and 49 (10%) for trichomonas. The acceptance for collecting penile swabs was high and the performance was higher than in urine for detecting chlamydia and gonorrhea. The program has expanded to now include MD, DC, WV, parts of IL, and Denver CO, with expansion planned soon to AK. In multivariable analyses, age, race, household income, and use of condoms were independently associated with infection with at least one STI. Of respondents, 34% had a prior STI;29% reported having a partner with an STI, but only 13% reported always using a condom. Seventy-seven percent of men preferred a self-administered specimen versus attending a clinic, 89% reported swab use was easy, and 89% would use internet-based screening again. This unique public health strategy can help reach persons, who do not have insurance, prefer confidentiality and privacy, and who do not have a family doctor. We have documented a decrease in the prevalence of both chlamydia and gonorrhea in an out reach program for pregnant women in Baltimore. At the beginning of the screening program, the prevalence of chlamydia was 18.2% but declined over the subsequent years to 8.7% in 2008. The prevalence of gonorrhea also declined significantly from a high of 9.1% to a low of 1.3% in 2008. Continuation of outreach screening and treatment programs can help reduce the prevalence of STDs in our community. We participated in surgical and antibiotic treatment intervention studies in Ethiopia, Niger, and Tanzania in efforts to control trachoma, the most common infectious cause of blindness worldwide. These studies have shown dramatic reductions in blindness in communities in which severe disease is first treated with surgery followed by community-wide azithromycin mass therapy. To determine whether infection recurs, we re-examined individuals in Tanzania five years after initiation of the program. Treatment coverage was 80% for all ages in the first year, although coverage 18 months later was lower at <70%. At five years, clinical trachoma rates were still lower than at baseline, ranging from 45% compared to 81% at baseline. Chlamydia infection rates at baseline were 71%, but declined to 27% five years after two rounds of mass therapy. In a new sub-study of the Tanzania program, we are studying the ancillary benefits of azithromycin in affecting chlamydia, gonorrhea, malaria, respiratory infections, and diarrhea.